This thesis describes the development of new methodologies promoted by bifunctional Brønsted basic H-bonding catalysis and Lewis basic organocatalysts. Chapter 2 describes the synthesis of novel chiral guanidines and their application as Brønsted and Lewis base catalysts in a variety of processes. Chapter 3 screens an array of Brønsted basic organocatalysts for the synthesis of trans-dihydrobenzofurans. A tertiary amine-thiourea bifunctional catalyst is used for an intramolecular Michael addition using keto-enones. The desired dihydrozofurans were obtained in excellent yield and with excellent diastereo- and good enantiocontrol. Chapter 4 describes the use of an isothiourea catalyst, HyperBTM, for the formal [2+2] cycloaddition between homohydrides and perfluorinated ketones to furnish β-lactones. The products were obtained in excellent yield and with excellent diastereo- and enantioselectivity. A large scope of 36 examples is reported. The derivatizion of the obtained β-lactones via ring-opening with a range of nucleophiles gave access to an array of β-hydroxycarbonyl compounds. Oxetanes could be accessed by a two step protocol, consisting of β-lactone reduction to give a diol, followed by cyclization. Chapter 5 describes a mechanic investigation on the isothiourea-catalysed formal [2+2] cycloaddition. A variable time normalisation graphical analysis method was used to determine the partial orders for anhydride, ketone and catalyst. The catalyst resting state was determined to be free catalysts by use of a fluorine-labelled catalysts.

M.Sc. / This study comprised the synthesis and characterization of new carbonyl carbene complexes of chromium, molybdenum and tungsten, prepared from thiazole precursors. In addition, the preparation and characterization of coordination compounds of chromium, tungsten and iron with new thiazole dithiocarboxylester ligands are reported.

The master´s thesis is focused on the characterization of degradation process of polypropylene and polypropylene with statistic copolymer into which manganese (II) stearate and cobalt (II) stearates were added at 0.05, 0.10 and 0.20 wt.% loadings. The aim of the thesis was to prepare the controlled life-time polypropylene. The degradation was studied at varying temperatures and prodegradant loadings. The prodegradants were synthetized and characterized using the FTIR and DSC techniques. Thermooxidation of the tested samples induced the changes in crystallinity, melting points and melt-flow indexes. Tensile strength and other mechanical properties were determined by means of the tensile test. The carbonyl index was determined using FTIR, the thermooxidation stability test was used to determine the activation energies of reactions. The changes in morphology of degraded samples were observed by SEM analysis.

Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Alžbeta Tomanová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Effect of selected tyrosine kinase inhibitors on the activity of human carbonyl reducing enzymes Key words: tyrosin kinases, screening, carbonyl, daunorubicin, inhibition Tyrosine kinases are a subclass of protein kinases, catalysing the transfer of ATP phosphate residue to a protein, thereby playing an important role in cellular signaling. Abnormal tyrosine kinase activity is present in various malignancies. In certain cases, inhibition of their function can prevent tumor cell proliferation and eventually induce apoptosis. At the same time, some tyrosine kinase inhibitors have demonstrated the ability to inhibit efflux transporters, which are often involved in the development of resistance to anticancer treatment. In this diploma thesis, the inhibitory effect of imatinib, nilotinib, dasatinib and acalabrutinib (tyrosine kinase inhibitors) has been studied on carbonyl reducing enzymes, whose overexpression by tumor cells may lead to resistance to chemotherapy. In particular, in the case of anthracyclines, the reduction of carbonyl group on C-13 results in not only lower cytotoxic activity, but also increased...

Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Petra Lakomá Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: The effect of alisertib and brigatinib on the activity of selected human carbonyl reducing enzymes Key words: brigatinib, alisertib, daunorubicin, inhibition, carbonyl-reducing enzymes Protein kinases are enzymes, whose main function is based on a transfer of phosphate group from ATP to protein substrate. This common posttranslational modification is involved in the regulation of intracellular processes and cell signaling. Altered expression of protein kinases is often coupled with a development of cancer. Inhibition of protein kinases may prevent cancer cell proliferation and induce their cell death. The main aim of the diploma thesis was to measure inhibition potential of protein kinase inhibitors, alisertib and brigatinib, against carbonyl-reducing enzymes. Overexpression of carbonyl-reducing enzymes in cancer cells may cause resistance to drugs followed by failure of chemotherapeutic therapy. In case of antracyclin chemotherapeutic daunorubicin, carbonyl-reducing enzymes reduce the carbonyl in C-13 giving rise a primary metabolite daunorubicinol, which has lower cytotoxic effect but higher cardiotoxicity. The effort to...

It is the purpose of this thesis to explore the experimental relationships which exist between Amberlite IR-45 and various carbonyl compounds with the hope that the knowledge obtained may ultimately form the basis of a new separation technique.

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Industrial processes generate large quantities of process and product quality data. Most of this data is stored and is analyzed in a univariate fashion. However important information may be lost through the implementation of univariate analysis methods. This information is contained in the correlation structure amongst the process and product quality variables and between these two types of variables. Through multivariate analysis this information is retained. As a result process evaluation, prediction and monitoring are more effectively performed. Multivariate data analysis techniques were therefore applied to data sets that summarized three of INCO's Copper Cliff smelting and refining processes. In the first instance the analysis of historical data pertaining to a batch leaching process was undertaken and the time required for leaching was predicted. In the second a multivariate soft sensor was developed in order to predict the concentration of nitric oxide contained in the feed gas to the smelter acid plant. The final project involved the analysis and monitoring of a continuous nickel carbonyl process. The resulting models were evaluated and significant variables with respect to the variation in the process and product quality data and the correlation between them were identified. The product quality data was also well predicted using new process data only that was input to the models. Finally new data was input to the models and the process was monitored using a reduced number of latent variables. Contribution plots were used to identify the original variables that contributed most to the observations that exceeded the established control limits. / Thesis / Master of Science (MSc)

Thesis advisor: X. Peter Zhang / Highly strained three membered heterocycles are a common motif in many biologically relevant molecules and represent a versatile building block for organic synthesis. Of special interest for asymmetric synthesis is the construction of enantioenriched aziridines and epoxides, which are often used as chiral synthons to introduce heteroatoms in a stereoselective fashion. Among different elegant strategies, the direct aziridination and epoxidation of the ubiquitous alkene functionality represents one of the most powerful methods to access these motifs. Given the synthetic importance of the enantioenriched smallest aza- and oxaheterocycles, the focus of this dissertation is centered on the design and use of chiral cobalt porphyrins as catalysts to develop new methodologies for the asymmetric radical aziridination and epoxidation of alkenes.In the first part of this dissertation, we focused on using carbonyl azides as nitrogen source for the enantioselective radical aziridination of alkenes. Despite its high functionality and versatility for further derivatization, carbonyl azides have never been reported as nitrogen source for intermolecular asymmetric alkene aziridination. In the second part of this dissertation, we focused on opening up a new area of research, which involves the generation and characterization of the unprecedented cobalt porphyrin-supported oxygen-centered radical species. Finally, we demonstrated the synthetic utility of these new radical species by developing a new system for the asymmetric epoxidation of alkenes through the design and development of a novel family of catalyst named “JesuPhyrin”. / Thesis (PhD) — Boston College, 2021. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.